Five new cassane diterpenes from Myrospermum frutescens with activity against Trypanosoma cruzi.

Five novel cassane diterpenes (1-5) with activity against Trypanosoma cruzi were isolated from leaves of Myrospermum frutescens. The structures were determined as 18-hydroxycassan-13,15-diene (1), 6beta,18-dihydroxycassan-13,15-diene (2), 6beta-hydroxy-18-acetoxycassan-13,15-diene (3), 18-acetoxy-13,15-diene-19-cassanoic acid (4), and 6beta,13beta-dihydroxy-18-acetoxycassan-14(17),15-diene (5). Structures were elucidated by spectroscopic analysis (NMR and HRCIMS) and by the synthesis of derivatives 2a and 2b. Compounds 3 and 5 were more active against the extracellular form of the parasite (11 and 16 microM, respectively) than the intracellular forms, while compounds 1 and 2 were more active against the more clinically relevant intracellular forms of the parasite (17 microM). Compounds 1 and 2 were approximately 9-fold more toxic toward T. cruzi than toward human fibroblasts, the cell type that serves as the parasite's mammalian host cell.